tbuckley/cabot-search huggingface dataset:
Combined intraperitoneal and systemic chemotherapy as adjuvant or perioperative chemotherapy for patients with type 4 scirrhous gastric cancer: PHOENIX-GC2 trial.
Authors: Hironori Ishigami, Takeshi Omori, Yasushi Tsuji, Hisashi Shinohara, Hiroshi Yabusaki, Daisuke Kobayashi, Daisuke Takahari, Hiroaki Hata, Tetsuya Kusumoto, Mitsuro Kanda, Koji Oba, Joji Kitayama, Yasuyuki Seto
Journal: Journal of Clinical Oncology (2023)

TPS477 Background: Despite recent progress in adjuvant and perioperative chemotherapy, the prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combination chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a multicenter, open-label, randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Methods: Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled from 40 hospitals throughout Japan. Clinical trial information: jRCT2031200087 .
Short-term safety of adjuvant nivolumab therapy after neoadjuvant docetaxel plus cisplatin and 5-FU therapy for locally advanced esophageal squamous cell carcinoma.
Authors: Toshiharu Hirose, Shun Yamamoto, Toru Kadono, Go Ikeda, Akihiro Ohara, Mai Itoyama, Kazuki Yokoyama, Yoshitaka Honma, Koshiro Ishiyama, Junya Oguma, Hiroyuki Daiko, Ken Kato
Journal: Journal of Clinical Oncology (2023)

312 Background: CheckMate 577 trial demonstrated efficacy of adjuvant nivolumab (Ad-Nivo) therapy in locally advanced esophageal cancer patients (pts) who underwent surgery after neoadjuvant chemoradiotherapy and did not achieve pathologic complete response. In Japan, neoadjuvant docetaxel plus cisplatin, 5-FU (NeoDCF) therapy is the standard care for locally advanced resectable esophageal squamous cell carcinoma (ESCC) based on the results of the JCOG1109 study. The efficacy and safety of Ad-Nivo therapy after NeoDCF therapy were unknown, so guidelines recommendations have not been determined. Methods: The subjects of this retrospective study were pts with histologically confirmed resectable locally advanced ESCC who received Ad-Nivo (480mg/body, every 4 weeks for 12 times) after NeoDCF in our hospital from Jan 2022 to Sep 2022. We evaluated safety as adverse events during treatments and clinical outcomes. Results: Twenty pts were selected in this study. Characteristics were median age (range) 65 (51–75) years, male/female 70/30%, PS 0/1 85/15%, Ce/Ut/Mt/Lt 5/15/50/30%, clinical stage II/III/IVA/IVB (supraclavicular lymph node) 10/70/0/20%, pathological stage IIB/IIIA/IIIB/IVA/IVB 30/5/40/10/15%. The pathological response according to Japanese Classification of Esophageal Cancer was Grade 0/1a/1b/2/3 5/20/20/40/15%. Median time (range) from surgery to Ad-Nivo was 9 weeks (4-20 weeks). The adverse events included fatigue (30%), increase AST (30%), increase ALT (15%), pruritus (15%), hyperthyroidism (15%), diarrhea (10%), decreased appetite (10%), and pneumonitis (10%). Grade &gt;3 adverse events were not observed. Recurrence was observed in three pts (15%), which site was regional lymph node (2 pts of pathological stage III and IVB) and anastomosis (1pt of pathological stage IVA). Three pts with recurrence received definitive chemoradiotherapy, and still continue the treatment. Conclusions: The short-term toxicity of Ad-Nivo after NeoDCF was well-tolerated and acceptable.
Next-generation whole blood transcriptome-based assay for advanced adenoma detection.
Authors: Sahar Hosseinian Ehrensberger, Victoria Wosika, Noushin Hadadi, Sara Fonseca Costa, Eric Durandau, Sylvain Monnier-Benoit, Laura Ciarloni, Stefan J. Scherer, Sabine Tejpar
Journal: Journal of Clinical Oncology (2023)

77 Background: Colorectal Cancer (CRC) is the second leading cause of cancer mortality worldwide although highly curable if detected early. An accurate liquid biopsy test for early cancer and precancerous lesion, detection is key to promote prevention and reduce mortality. We previously developed a liquid biopsy test based on immune cells response to the tumor, commercialised under the name of Colox, with best-in-class clinical performances for AA detection (52% sensitivity and 92% specificity) (Ciarloni L et al, Clin Cancer Res, 2016). An improved second generation of the test, leveraging transcriptome profiling and advanced machine learning tools, is under development and first results are presented. Methods: Prospective peripheral whole-blood (PAXgene) samples from subjects diagnosed with CRC, advanced adenoma (AA), non-advanced adenoma, other types of cancer as well as controls without colorectal neoplasia (CON) were divided into discovery and validation sets. Transcriptome profiles were generated by RNA-seq and gene expression signatures identified leveraging Novigenix’s proprietary LITOseek platform, which integrates several advanced Machine Learning (ML) methods into a ranking systems. Biological functional analysis was performed by over-representation (ORA), gene set enrichment (GSEA) and gene network analyses (STRINGdb). Results: Significant changes in the whole blood transcriptome profile of AA compared to CON were identified. Functional analysis highlighted upregulation of fatty acid derivative biosynthesis, interferon signaling, tryptophan catabolism to kynurenine, and downregulation of DNA repair in AA blood samples compared to CON. A novel gene classifier was generated, showing for AA detection 71% sensitivity, 94% specificity and an AUC of 74% by cross-validation on the discovery set. Validation of the gene classifier in an independent set is currently ongoing and will be presented at the congress. Conclusions: Capturing immune-related information using whole blood trascriptome profiling and applying cutting-edge machine learning technologies demonstrated to be valuable for identifying gene signatures for advanced adenoma detection. This differentiated solution has demonstrated best-in-class potential to significantly improve patient outcomes by detecting precancerous lesions with a simple non-invasive blood test.
Real-world data in 1000 patients with unresectable hepatocellular carcinoma (HCC) treated with systemic therapy: Patient background in PRISM study.
Authors: Masafumi Ikeda, Shinji Itoh, Ryosuke Tateishi, Tatsuya Yamashita, Takuji Okusaka, Naoya Kato, Junji Furuse, Masatoshi Kudo
Journal: Journal of Clinical Oncology (2023)

566 Background: Systemic therapy is one of the most important treatment modalities for unresectable hepatocellular carcinoma (HCC). At present, six regimens, except durvalumab plus tremelimumab, are reimbursable for the treatment of HCC in Japan. In clinical practice, there are various patient backgrounds and patterns in the treatment sequence of systemic therapy. Therefore, a prospective, observational, large-scale multicenter study of systemic therapy for HCC (PRISM) was conducted to establish real-world evidence from real-world data in Japan. Methods: Patients with histologically or clinically diagnosed HCC, with no prior systemic therapy, with written informed consent were consecutively enrolled into the study. The primary endpoint is overall survival, and the secondary endpoints are the progression-free survival, time-to-treatment failure, grade 3-4 adverse events, and proportion of transition to subsequent treatment; all endpoints are calculated by each regimen/treatment line. The planned sample size is 1,000 patients with an enrollment and follow-up period of 2 years each. Clinical trial registration: UMIN000040488. Results: From August 2020 to July 2022, the enrollment of 1,000 patients was completed in 42 participant hospitals in Japan. As of Sep 2022, the 1000 patients’ background data have been collected. The median age with range was 73 years (30-93). ECOG performance status was 0 in 612 patients (77.9%), and Child-Pugh score was 5 points in 358 (50.2%) and 6 in 226 (31.7%). BCLC stage was B in 277 patients (36.9%) and C in 391 patients (52.1%). 210 patients (26.8 %) and 207 patients (26.4%) had portal vein tumor thrombosis and extrahepatic metastasis, respectively. The median AFP level was 33 ng/mL (range: 1.1- 524878.9). As first-line therapy, atezolizumab plus bevacizumab was selected in 650 (82.5%), lenvatinib in 116 (14.7%), and sorafenib in 15 (1.9%) patients. Conclusions: The analysis of these real-world data of systemic therapy for patients with unresectable HCC could help clarify the treatment outcomes in clinical practice, and is expected to be broadly applicable to real-world evidence in all Japan. Clinical trial information: UMIN000040488 .
Safety and efficacy from the phase 1 SURPASS trial of ADP-A2M4CD8, a next-generation T-cell receptor T-cell therapy, in patients with advanced esophageal, esophagogastric junction, or gastric cancer.
Authors: Mariela A. Blum Murphy, Jaffer A. Ajani, Brian Andrew Van Tine, Jeffrey Melson Clarke, Marcus O. Butler, Donald P. Lawrence, Melissa Lynne Johnson, Andres Cervantes, Victor Moreno, David S. Hong, Francine Elizabeth Brophy, Jean-Marc Navenot, Quan Lin, Jose Saro, Elliot Norry
Journal: Journal of Clinical Oncology (2023)

349 Background: ADP-A2M4CD8 is a specific peptide enhanced affinity receptor mixed CD4+ and CD8+ T-cell therapy targeting the cancer testis antigen MAGE-A4 and modified with addition of a CD8α co-receptor designed to provide additional functionality to CD4+ T-cells. ADP-A2M4CD8 has demonstrated a favorable benefit to risk profile in the Phase 1 SURPASS trial (NCT04044859) in HLA A*02–eligible patients (pts) with unresectable or metastatic tumors positive for MAGE-A4 (Hong DS, et al. E-poster 540P: ESMO 2021; Virtual). Here we report updated clinical outcomes in pts with esophageal, esophagogastric junction (EGJ), or gastric cancer. Methods: SURPASS is a first-in-human trial consisting of a modified 3+3 dose-escalation design and an expansion cohort. Autologous T-cells are obtained by leukapheresis, transduced with a self-inactivating lentiviral vector expressing the MAGE-A4-specific T-cell receptor and the CD8α co-receptor, and infused back to the pts as ADP-A2M4CD8 following lymphodepleting chemotherapy. Primary and secondary objectives are safety and anti-tumor activity, respectively. Results: As September 6, 2022, 13 pts (11 male, 2 female) with esophageal (3), EGJ (8), and gastric cancer (2) received ADP-A2M4CD8 (range: 1.02–9.9x10 9 transduced T-cells). All pts had adenocarcinoma, median age was 55 years (range: 31–71), median MAGE-A4 expression H-score was 245 (range: 160–300), and pts received median of 2 lines of prior therapy (range 1–5). Adverse events (AEs) were consistent with those typically associated with lymphodepleting chemotherapy, cellular therapy, and/or disease. One pt had a Grade 5 (fatal) AE of pancytopenia. Overall response rate per RECIST v1.1 by investigator review was 15% (2 partial response [PR]). Disease control rate was 77% (2 PR+8 stable disease). This trial is ongoing, and additional data will be presented. Conclusions: Results indicate an acceptable benefit to risk profile and encouraging anti-tumor activity of ADP-A2M4CD8. An additional treatment cohort has been included in the updated SURPASS trial protocol to evaluate ADP-A2M4CD8 combined with nivolumab. A Phase 2, open-label trial in advanced esophageal and EGJ cancers has been initiated (SURPASS-2; NCT04752358). Clinical trial information: NCT04044859 .
A phase II study of CAPOXIRI as a neoadjuvant chemotherapy in patients with locally advanced rectal cancer (Colorectal Cancer Treatment Group, MSCSGO).
Authors: Yoshinori Kagawa, Chu Matsuda, Toshihiro Kudo, Yoshihiro Morimoto, Mitsuyoshi Tei, Yoshihito Ide, Norikatsu Miyoshi, Hidekazu Takahashi, Mamoru Uemura, Ichiro Takemasa, Taroh Satoh, Tsunekazu Mizushima, Kohei Murata, Yuichiro Doki, Hidetoshi Eguchi
Journal: Journal of Clinical Oncology (2023)

109 Background: Addition of perioperative multi-agent chemotherapy to the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. We conducted a multicenter single-arm phase II study to evaluate the safety and efficacy of capecitabine combined with oxaliplatin and irinotecan (CAPOXIRI) as triplet neoadjuvant chemotherapy in patients with LARC. Methods: The key eligibility criteria were as follows: (1) age over 20 years; (2) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; (3) resectable clinical stage II (T3 or T4 with N0) or III (any T and N1–3), with the primary tumor located within 12 cm of the anal verge. Patients received intravenous oxaliplatin (85 mg/m 2 ) and intravenous irinotecan (150 mg/m 2 ) on day 1 and oral capecitabine (1,000 mg/m 2 ) twice daily on days 1–7 followed by 7 days of rest, repeated every 2 weeks for six cycles. Total mesothelial resection was performed 4–8 weeks after chemotherapy ended. In addition to the treatment protocol, patients received adjuvant chemotherapy for four cycles. The primary study endpoint was the pathological complete response (pCR) rate. We based the sample size of the study described herein on an expected pCR rate of 18% and a threshold pCR rate of 5% to detect differences at a two-sided alpha error of 0.05 and a statistical power of 0.2. Results: Between June 2013 and December 2016, 55 patients were enrolled in the study. Forty-five (83.3%) of the 54 patients who underwent NAC received the full six courses. Fifty-two (94.5%) patients underwent tumor resection. Laparoscopic surgery was performed in 47 (90.4%) patients, and lateral lymph node dissection was performed in 35 (67.3%) patients. Forty-nine (94.2%) patients underwent R0 resection. The pCR rate was 7.7% (95% CI 3.0% to 18.2%). The 3-year local recurrence rate was 3.9%, the 3-year disease-free survival (DFS) rate was 77.3, and the 3-year overall survival rate was 96.0%. NAC-related grade 3/4 adverse event rates were as follows: neutropenia (25.9%), anorexia (13.0%), diarrhea (11.1%) and anemia (7.4%). Conclusions: CAPOXIRI neoadjuvant chemotherapy appears to be feasible and efficacious for patients with LARC. Although neoadjuvant XELOXIRI alone did not yield our expected pCR rate, the local recurrence rate, 3-year DFS and measures of safety met current standards. Clinical trial information: UMIN000009974 .
Survival benefit and optimal timing for re-resection in patients with gallbladder cancer: A National Cancer Database analysis.
Authors: Shivani Shah, Ryan Sweeney, Rodney E. Wegner
Journal: Journal of Clinical Oncology (2023)

614 Background: Often times, gallbladder cancer is diagnosed incidentally after cholecystectomy. Most patients will then undergo re-resection for potential residual disease, however overall survival (OS) benefit data in this scenario is variable. Further, limited literature regarding optimal time to re-resection exists. Prior studies found the optimal time to re-resection to be approximately 4-8 weeks after initial diagnosis; however, additional data is needed to further validate these findings. In this National Cancer Database(NCDB) analysis we compare OS in patients diagnosed with T1b – T3 gallbladder cancer who underwent re-resection and evaluate if time to resection impacts OS. Methods: We reviewed the NCDB for patients who had received initial cholecystectomy for gallbladder cancer and were subsequently eligible for re-resection based on tumor stage (T1b-T3 disease) from 2004-2018. We excluded patients with metastatic M1 disease and T0, T1a, T1, or T4 disease. Patients with re-resection were further subdivided into four cohorts based on time to re-resection: 0-4 weeks, 5-8 weeks, 9-12 weeks and &gt;12 weeks. We used a Cox proportional hazards ratio to identify factors associated with worse survival and logistic regression to evaluate characteristics associated with re-resection. OS was calculated using Kaplan Meier curves. Results: 791 (5.82%) patients received re-resection of 13,601patients meeting inclusion and exclusion criteria. Cox proportional hazards analysis showed a Comorbidity Score of 1 was associated with worse survival. Patients with higher Comorbidity Scores (1,2, or 3) and treatment at comprehensive community, integrated or academic cancer programs were less likely to undergo re-resection (in comparison to community programs). Patients treated at an Urban facility or diagnosed from 2009-2018 were more likely to undergo re-resection. The cohort with no re-resection had the lowest median OS [17.61 months; CI 17.05- 18.20] and re-resection showed significantly improved OS [HR 0.87; 95 CI 0.77-0.98; p=0.02]. Significantly improved survival was noted when re-resection was completed at 5-8 weeks [HR 0.67; CI 0.57- 0.81], 9-12 weeks [HR 0.64; CI 0.52- 0.79], or &gt;12 weeks [HR 0.61; CI 0.47- 0.78]. Conclusions: Despite the retrospective nature and small sample size of our study, the results are consistent with prior studies depicting a survival benefit with re-resection. Additionally, optimal timing to re-resection supports previous data showing a clear benefit at any time &gt;4 weeks. However, there was no significant survival difference as to whether re-resection was completed at 5-8 weeks, 9-12 weeks, or &gt; 12 weeks post initial cholecystectomy. Decreased post-operative inflammation and accurate staging at &gt;4 weeks may account for improved survival with later re-resection; however, future investigations are warranted to delineate underlying causes.
Factors associated with weekend emergency department visits in patients with GI cancer.
Authors: Jay Parekh, Victor Lee, Aslihan Yerlikaya, Soniya Abraham, Henry Soo-Min Park, Stacey Stein, Vikram Jairam
Journal: Journal of Clinical Oncology (2023)

813 Background: Gastrointestinal (GI) cancers account for highest ED revisits among cancer patients. Weekend ED visits are also associated with higher mortality. We aimed to analyze factors associated with weekend ED visits among GI cancer patients. Methods: Nationwide Emergency Department Sample (NEDS) database was queried from 2009 to 2017 for ED visits with GI primary tumor. ED visits were characterized by demographic, socioeconomic factors, hospital characteristics and primary cancer. Univariate and multivariate logistic regression were performed. Data was analyzed using Stata. Results: From 2009 to 2017, 6,862,077 ED visits associated with GI cancer were analyzed and 1,811,111(26.4%) visits were on weekend. Weekend visits were associated with increased in-hospital mortality (odds ratio [OR] 1.06; 95% Confidence Interval [CI] 1.04-1.). Weekday mortality was 3.8%, while weekend was 3.9%. Weekend visits were negatively associated with presentation in 2013-2017 as compared to 2009-2012 (OR 0.96; 0.95-0.97), Northeast hospitals (OR 0.89; 0.88-0.91) compared to Midwest, teaching hospital status (OR 0.96; 0.95-0.97) compared to non-teaching and metastatic cancer (OR 0.96; 0.95-0.97) compared to non-metastatic cancers. Compared to colon, weekend admissions were also negatively associated with anorectal (OR 0.96; 0.95-0.98) and hepatobiliary cancers (OR 0.96; 0.95-0.98). Conclusions: Presentation between 2013 to 2017, teaching hospital status, Northeast hospitals and metastatic stage were associated with fewer weekend ED visits. These findings could be potentially explained by increased and primary care utilization. There was a statistically significant association between mortality and weekend admissions, however the absolute difference was only 0.1%. Possible explanations include potential differences in staffing, interventions and procedures over the weekends compared to weekdays. In comparison to colon, anorectal and hepatobiliary cancer patients are less likely to have weekend ED visits while pancreatic cancer patients are more likely to have weekend ED visits. Our findings may help GI oncologists identify patients at risk of weekend ED visits.[Table: see text]
Real-world dosing of regorafenib in patients with unresectable hepatocellular carcinoma (uHCC): Final analysis of the prospective, observational REFINE study.
Authors: Richard S. Finn, Philippe Merle, Masafumi Ikeda, Heinz-Josef Klümpen, Gianluca Masi, Alessandro Granito, Ho Yeong Lim, Masatoshi Kudo, Shukui Qin, René Gerolami, Yi-Hsiang Huang, Do Young Kim, Matthias Pinter, Naoya Kato, Masayuki Kurosaki, Kazushi Numata, Javeed Khan, Kirhan Ozgurdal, Yoon Jun Kim
Journal: Journal of Clinical Oncology (2023)

518 Background: Final results from the real-world REFINE study confirmed the safety and effectiveness of regorafenib (REG) in a broad population of patients (pts) with uHCC that was consistent with the results from RESORCE, in which REG prolonged overall survival (OS) vs placebo in pts with uHCC who progressed on prior sorafenib. Here we evaluate baseline characteristics and outcomes according to the initial REG dose. Methods: REFINE (NCT03289273), an international, prospective, multicenter study, enrolled pts with uHCC for whom a decision to treat with REG was made by the treating physician prior to enrollment according to the local health authority approved label (160 mg/day, 3 weeks on/1 week off). The primary objective was safety (NCI-CTCAE v4.03); secondary endpoints included OS and progression-free survival (PFS). Results: Of 1005 pts eligible for analysis, 47%, 11%, 40%, and 3% initiated REG at 160 mg, 120 mg, 80 mg, and 40 mg, respectively. A higher proportion of pts from Asia initiated REG at 160 mg (51%) vs non-Asian countries (42%), and 67% were Child–Pugh A in Asia vs 54% in non-Asian countries at study entry. Pts initiating REG at 160 mg were more likely to be Child–Pugh A and albumin–bilirubin (ALBI) grade 1 vs pts initiating REG at &lt;160 mg (Table). A higher proportion of pts (53%) who initiated REG at 160 mg ended prior sorafenib at 800 mg/day. Of the pts intolerant to prior sorafenib (n=91), more pts started REG at 80 mg (49%), followed by 160 mg (32%) and 120 mg (9%). Median duration of REG treatment was similar across initial dose levels (overall 3.7 months). Any-grade TEAEs were reported for 90%, 93%, and 93% of pts initiating REG at 160 mg, 120 mg, and 80 mg, respectively. TEAEs led to dose modifications in 49%, 51%, and 38% and to dose reductions in 34%, 26%, and 17% of pts. Median OS was 15.8 months in pts who initiated REG at 160 mg, 13.3 months at 120 mg, and 11.1 months at 80 mg. Median PFS was similar across doses (overall 3.9 months). Conclusions: In this real-world study, most pts with uHCC initiated REG at 160 mg or 80 mg/day. A higher proportion of pts from Asia initiated REG at the recommended dose, and a higher proportion of pts initiating REG at 160 mg had relatively better liver function at study entry. Safety was generally similar regardless of initial dose, and OS was observed to be longer in pts initiating REG at 160 mg vs lower doses. Clinical trial information: NCT03289273 . [Table: see text]